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Background and aims: Alagille syndrome (ALGS) is a multisystem disorder, characterized by cholestasis. Existing outcome data are largely derived from tertiary centers, and real-world data are lacking. This study aimed to elucidate the natural history of liver disease in a contemporary, international cohort of children with ALGS. Approach and results: This was a multicenter retrospective study of children with a clinically and/or genetically confirmed ALGS diagnosis, born between January 1997 and August 2019. Native liver survival (NLS) and event-free survival rates were assessed. Cox models were constructed to identify early biochemical predictors of clinically evident portal hypertension (CEPH) and NLS. In total, 1433 children (57% male) from 67 centers in 29 countries were included. The 10 and 18-year NLS rates were 54.4% and 40.3%. By 10 and 18 years, 51.5% and 66.0% of children with ALGS experienced >= 1 adverse liver-related event (CEPH, transplant, or death). Children (>6 and = 5.0 and = 10.0 mg/dl had an 8.0-fold (95% CI, 3.4-18.4) increased risk of developing CEPH compared with those 10.0 mg/dl were associated with a 4.8 (95% CI, 2.4-9.7) and 15.6 (95% CI, 8.7-28.2) increased risk of transplantation relative to = 5.0 mg/dl, with 79% reaching adulthood with native liver (p < 0.001). Conclusions: in this large international cohort of ALGS, only 40.3% of children reach adulthood with their native liver. A TB, This study received funding support from the following agencies: The Alagille Syndrome Alliance, Mirum Pharmaceuticals Inc. and Albireo Pharma, Inc. who provided unrestricted educational grants to the Hospital for Sick Children (SickKids Foundation). The study sponsors were not involved in the conduct of the research study or preparation of the manuscript.

Progressive familial intrahepatic cholestasis type 1 (PFIC1) results from biallelic pathogenic variants in ATP8B1. This study sought second pathogenic variants in ATP8B1 by whole-genome sequencing (WGS) in four unrelated low γ-glutamyl transpeptidase cholestasis patients in whom clinical suspicion of PFIC1 was high and gene-panel or Sanger sequencing had identified only one pathogenic variant in ATP8B1. Sanger sequencing confirmed WGS findings and determined the origin of each variant. Novel nonrecurrent structural variants in three patients (patient 1 to patient 3) were identified in trans: g.55396652_55403080del (6427-bp deletion), g.55335906_55346620dup (10,715-bp duplication), and g.55362063_55364293dup (2231-bp duplication). One synonymous variant in patient 4 was recognized in trans (c.1029GA, p. Thr343Thr) and demonstrated as deleterious. In conclusion, WGS improves genetic diagnostic yield in PFIC1. These findings expand the gene-variant spectrum associated with familiar intrahepatic cholestasis 1 (FIC1) disease and for the first time report tandem duplication in ATP8B1 associated with cholestasis.

Epigenetic regulation is important for cancer tumor metastasis and progression, including lung and liver cancer. However, the mechanism of epigenetic regulation in liver cancer leaves much to be discussed. According to a previous study, p300/CBP‐associated factor (PCAF) mediated epithelial–mesenchymal transition (EMT) and promotes cancer metastasis by recruiting intestine‐specific homeobox (ISX) and bromodomain‐containing protein 4 (BRD4) in lung cancer. To figure out whether the three genes are also expressed in patients with hepatocellular carcinoma (HCC) or not, and their correlation with patients’ outcome, BRD4, PCAF, and ISX messenger RNA (mRNA) expression levels in 377 patients with HCC were investigated using quantitative polymerase chain reaction and confocal fluorescence imaging. The correlation of the gene expression (PCAF, ISX, and BRD4) in liver cancer is also being investigated. Here, we show that the mRNA expression of PCAF, BRD4, and ISX in 377 paired specimens from patients with HCC, and the adjacent normal tissues exhibited a tumor‐specific expression pattern, highly correlated with disease pathogenesis, patient survival time, progression stage, and poor prognosis. The results show that ISX and BRD4 can potentially be a target for improving the survival rate., ISX and BRD4 can potentially be a target for improving the survival rate.

Background Wolbachia technology is a novel vector control approach that can reduce mosquito populations and the risk of mosquito-borne diseases, which has recently gained popularity amongst countries. In 2016, Singapore embarked on a multi-phased field study named Project Wolbachia – Singapore, to evaluate the use of Wolbachia technology as an Aedes aegypti mosquito population suppression tool to fight dengue. Due to the novelty of this technology in Singapore, this study aims to understand the public’s acceptance and sentiments towards the use of Wolbachia technology. Methods Several public sentiment survey approaches – including online, face-to-face in the streets, as well as door-to-door household surveys – were conducted. Results The surveys conducted prior to the first field releases and implementation of the project revealed high support for the use of Wolbachia technology in Singapore. A household perception survey conducted in the interim of the first project phase was encouraging, with the majority of the respondents being aware of the project and having no concerns with the release of male Wolbachia-carrying Aedes aegypti (Wolbachia-Aedes) mosquitoes in their neighbourhood. Conclusions The study reveal high support for the use of Wolbachia technology in Singapore and also provided invaluable insights that were used in the development of a public communications and engagement framework model, which thus helped to guide these elements in the subsequent phases and expansion of the project.

METTL3 increasing the mature miRNA levels via N6-Methyladenosine (m6A) modification of primary miRNA (pri-miRNA) transcripts has emerged as an important post-transcriptional regulation of miRNA biogenesis. Our previous studies and others have showed that muscle specific miRNAs are essential for skeletal muscle differentiation. Whether these miRNAs are also regulated by METTL3 is still unclear. Here, we found that m6A motifs were present around most of these miRNAs, which were indeed m6A modified as confirmed by m6A-modified RNA immunoprecipitation (m6A RIP). However, we surprisingly found that these muscle specific miRNAs were repressed instead of increased by METTL3 in C2C12 in vitro differentiation and mouse skeletal muscle regeneration after injury in vivo model. To elucidate the underlined mechanism, we performed reporter assays in 293T cells and validated METTL3 increasing these miRNAs at post-transcriptional level as expected. Furthermore, in myogenic C2C12 cells, we found that METTL3 not only repressed the expression of myogenic transcription factors (TFs) which can enhance the muscle specific miRNAs, but also increased the expression of epigenetic regulators which can repress these miRNAs. Thus, METTL3 could repress the muscle specific miRNAs at transcriptional level indirectly. Taken together, our results demonstrated that skeletal muscle specific miRNAs were repressed by METTL3 and such repression is likely synthesized transcriptional and post-transcriptional regulations.

Context Elevated levels of plasma leucine-rich α-2-glycoprotein 1 (LRG1), a component of transforming growth factor beta signaling, are associated with development and progression of chronic kidney disease in patients with type 2 diabetes (T2D). However, whether this relationship is causal is uncertain. Objectives To identify genetic variants associated with plasma LRG1 levels and determine whether genetically predicted plasma LRG1 contributes to a rapid decline in kidney function (RDKF) in patients with T2D. Design and participants We performed a genome-wide association study of plasma LRG1 among 3694 T2D individuals [1881 (983 Chinese, 420 Malay, and 478 Indian) discovery from Singapore Study of Macro-angiopathy and Micro-vascular Reactivity in Type 2 Diabetes cohort and 1813 (Chinese) validation from Diabetic Nephropathy cohort]. One- sample Mendelian randomization analysis was performed among 1337 T2D Chinese participants with preserved glomerular filtration function [baseline estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2)]. RDKF was defined as an eGFR decline of 3 mL/min/1.73 m2/year or greater. Results We identified rs4806985 variant near LRG1 locus robustly associated with plasma LRG1 levels (meta P = 6.66 × 10−16). Among 1337 participants, 344 (26%) developed RDKF, and the rs4806985 variant was associated with higher odds of RDKF (meta odds ratio = 1.23, P = 0.030 adjusted for age and sex). Mendelian randomization analysis provided evidence for a potential causal effect of plasma LRG1 on kidney function decline in T2D (P Conclusion We demonstrate that genetically influenced plasma LRG1 increases the risk of RDKF in T2D patients, suggesting plasma LRG1 as a potential treatment target. However, further studies are warranted to elucidate underlying pathways to provide insight into diabetic kidney disease prevention.

OBJECTIVES/HYPOTHESIS The routine practices of examining submucosal lesions are not suitable for deep lesions. Therefore, we evaluated the efficacy of non-real-time image-guided transnasal endoscopic fine-needle aspiration biopsy (FNAB) in diagnosing nasopharyngeal carcinoma (NPC) with submucosal lesions. STUDY DESIGN The effectiveness evaluation of diagnostic methods. METHODS Fifty suspected NPC patients who failed in conventional biopsies were enrolled in this study. The efficacy, maneuverability, and safety of FNAB in diagnosing these intractable cases were evaluated. RESULTS The definitive diagnostic results of these 50 patients were NPC (34/50, 68.0%), nasopharyngeal necrosis (1/50, 2.0%), nasopharyngeal mucositis (12/50, 24.0%), and other cancers (3/50, 6.0%), respectively. The results of the diagnostic efficacy of FNAB were sensitivity, 89.2%; specificity, 100.0%; positive predictive value, 100.0%; negative predictive value, 76.5%; and accuracy, 92.0%, respectively. The area under the receiver operating characteristic curves was 0.946 (95% confidence interval = 0.884-1.00, P

Background Reports showed that elevated proinflammatory cytokines, as detected in patients with psoriasis, was noted in individuals with major depressive disorder (MDD). Therefore, this study aimed to clarify the association of MDD and prospective incidence of psoriasis in human using a nationwide study. Method This population-based cohort study used the data from the Taiwan National Health Insurance system. 64,486 patients were defined as MDD cohort and 64,486 propensity score matched subjects without MDD were identified as comparison cohort. Each patient was independently tracked for a 5-year study period to assure them for a psoriasis diagnosis after the index date. Stratified Cox proportional hazard models were used to calculate the hazard ratio (HRs) for 5-year psoriasis risk. Results After adjustments, the HR of psoriasis for MDD patients was 1.32 compared with subjects without MDD. The stratified analyses present that MDD patients had approximately 1.30-fold significantly higher risk of psoriasis than comparison subjects in most subgroups. Furthermore, compared with the matched subjects without MDD, the adjusted HRs of psoriasis in the 2-, 3-, 4- and 5-year study periods were 1.33, 1.32, 1.33 and 1.32, respectively. Limitations Several patients with MDD or psoriasis might not include in this study, because of using a medical claims database. Conclusions This study provides population-based evidence that MDD is an independent risk factor of developing psoriasis, with an increased risk in the male sex. Additional investigations verifying our findings and exploring possible pathological mechanisms would be of great interest and value to the psychiatric field.

Background No reports are available on the technical efficiency and therapeutic response of virtual navigation (VN)-guided radiofrequency ablation (RFA) for patients with recurrent hepatocellular carcinoma (HCC) after hepatic resection. The aim of this study was to investigate the overall technical performance and outcome of VN-guided RFA in recurrent HCC patients. In addition, a nomogram model was developed to predict the factors influencing the overall survival (OS). Methods This was a prospective study on 76 recurrent HCC patients who underwent VN-guided RFA between June 2015 and February 2018. The technical feasibility, success, and efficiency, OS, local tumor progression, and complications were evaluated. A multivariate Cox regression analysis was conducted to predict the significant factors, and a nomogram including independent predictive factors was subsequently plotted to predict OS. Results The technical feasibility, success, and efficiency rates of VN-guided RFA were 86.4%, 94.7%, and 97.4%, respectively. The cumulative OS rates at 1-, 2-, and 3-year were 88.1%, 79.7%, and 71.0%, respectively. The cumulative local tumor progression rates at 1-, 2-, and 3-year were 5.5%, 8.7%, and 14.0%, respectively. In addition, the minor and major complication rates were 5.3% and 3.9%, respectively. No intervention-related deaths occurred during the follow-up period. The C-index of the OS nomogram in this study was 0.737. Conclusions VN-guided RFA is an effective therapeutic option in recurrent HCC patients and improves the long-term outcomes especially for the lesions that cannot be detected in the two-dimensional ultrasound. Besides, the nomogram may be a useful supporting tool in predicting OS to estimate the individual survival probability, optimize treatment options, and facilitate decision-making.

PURPOSE The coronavirus disease 2019 (COVID-19) pandemic has had a global impact, and Singapore has seen 33,000 confirmed cases. Patients with cancer, their caregivers, and health care workers (HCWs) need to balance the challenges associated with COVID-19 while ensuring that cancer care is not compromised. This study aimed to evaluate the psychological effect of COVID-19 on these groups and the prevalence of burnout among HCWs. METHODS A cross-sectional survey of patients, caregivers, and HCWs at the National Cancer Centre Singapore was performed over 17 days during the lockdown. The Generalized Anxiety Disorder-7 and Maslach Burnout Inventory were used to assess for anxiety and burnout, respectively. Self-reported fears related to COVID-19 were collected. RESULTS A total of 624 patients, 408 caregivers, and 421 HCWs participated in the study, with a response rate of 84%, 88%, and 92% respectively. Sixty-six percent of patients, 72.8% of caregivers, and 41.6% of HCWs reported a high level of fear from COVID-19. The top concern of patients was the wide community spread of COVID-19. Caregivers were primarily worried about patients dying alone. HCWs were most worried about the relatively mild symptoms of COVID-19. The prevalence of anxiety was 19.1%, 22.5%, and 14.0% for patients, caregivers, and HCWs, respectively. Patients who were nongraduates and married, and caregivers who were married were more anxious. The prevalence of burnout in HCWs was 43.5%, with more anxious and fearful HCWs reporting higher burnout rates. CONCLUSION Fears and anxiety related to COVID-19 are high. Burnout among HCWs is similar to rates reported prepandemic. An individualized approach to target the specific fears of each group will be crucial to maintain the well-being of these vulnerable groups and prevent burnout of HCWs.

Background and aims Obesity often initiates or coexists with certain metabolic abnormalities. This study sought to examine the independent and joint relations of weight and metabolic syndrome (MetS) with incident chronic kidney disease (CKD) among Chinese elderly people. Methods and Results A total of 15 229 participants (mean age: 62.8 years) from the Dongfeng-Tongji Cohort with complete baseline questionnaire and medical examination data were followed from 2008-2010 to 2013. All participants were categorized into four phenotypes: metabolically healthy non-overweight/obesity (MHNO), metabolically healthy overweight/obesity (MHO), metabolically unhealthy non-overweight/obesity (MUNO), metabolically unhealthy overweight/obesity (MUO). Multivariable-adjusted logistic regression models were applied to estimate the odds ratios (ORs) and confidence intervals (CIs) of four phenotypes with the risk of incident CKD, which was defined as estimated glomerular filtration rate (eGFR) 60 years or with baseline diabetes. Conclusion Both overweight/obesity and MetS were associated with an increased risk of CKD. It's worth noting that MHO and MUNO also have an elevated risk. Maintaining both normal weight and healthy metabolic profile is recommended.

Objective This study aimed to select optimal candidates benefiting from the addition of induction chemotherapy (IC) to concurrent chemoradiotherapy (CCRT) in stage II–IVa nasopharyngeal carcinoma (NPC) based on Epstein–Barr virus (EBV) DNA and nodal maximal standardized uptake values (SUVmax‐N) of [18F]‐fluorodeoxyglucose positron emission tomography. Patients and materials A total of 679 patients diagnosed with stage II–IVa (except N0) NPC were retrospectively included in this study. Overall survival was the primary endpoint. Survival differences between different groups were compared using the log‐rank test. The hazard ratio (HR) and 95% confidence interval (CI) were calculated using a multivariable Cox proportional hazards model. Results Both high levels of EBV DNA (>1500 copies/mL) and SUVmax‐N (>12.3) indicated worse survival conditions. All patients were divided into low‐ and high‐risk groups based on these two biomarkers. The risk group was an independent prognostic factor in OS, progression‐free survival (PFS), and distant metastasis‐free survival (DMFS) (all p‐values, Our study has demonstrated that EBV DNA and SUVmax‐N could serve as biomarkers to stratify NPC patients and guide physicians to select those who benefit from IC. Our findings provide important information for personalizing NPC treatment. Prospective clinical trials are warranted to evaluate the results of this study.

Limited evidence supports the use of early endpoints to evaluate the success of initial treatment of extranodal NK/T-cell lymphoma (ENKTCL) in the modern era. We aim to analyze progression-free survival at 24 months (PFS24) and subsequent overall survival (OS) in a large-scale multicenter cohort of patients. 1790 patients were included from the China Lymphoma Collaborative Group (CLCG) database. Subsequent OS was defined from the time of PFS24 or progression within 24 months to death. OS was compared with age- and sex-matched general Chinese population using expected survival and standardized mortality ratio (SMR). Patients who did not achieve PFS24 had a median OS of 5.3 months after progression, with 5-year OS rate of 19.2% and the SMR of 71.4 (95% CI, 62.9–81.1). In contrast, 74% patients achieved PFS24, and the SMR after achieving PFS24 was 1.77 (95% CI, 1.34–2.34). The observed OS rate after PFS24 versus expected OS rate at 5 years was 92.2% versus 94.3%. Similarly, superior outcomes following PFS24 were observed in early-stage patients (5-year OS rate, 92.9%). Patients achieving PFS24 had excellent outcome, whereas patients exhibiting earlier progression had a poor survival. These marked differences suggest that PFS24 may be used for study design and risk stratification in ENKTCL.

OBJECTIVE To assess and compare fetal loss rates before 28 weeks of singleton and twin pregnancies after mid-trimester amniocentesis. METHOD This historic cohort study included 13 773 women with singletons and 426 women with twins undergoing mid-trimester amniocentesis from 1/2015 to 3/2017. Pregnancies resulting in termination or selective reduction before 28 weeks were excluded, as well as twin gestations undergoing single-puncture amniocentesis. Fetal loss rates were compared between singleton and twins taking into account maternal characteristics, amniocentesis procedure, and fetal chromosomal abnormalities. RESULTS The rates of fetal chromosomal abnormalities were similar in singleton and twin gestations (1.13% vs 0.70%, P = .253). No difference was found in maternal or fetal characteristics, or amniocentesis procedure between the two groups. The fetal loss rate was significantly higher in twin compared with singleton pregnancies (1.91% vs 0.24%, P

The aim of this study was to pre-operatively investigate the diagnostic performance of 2D shear wave elastography (2D-SWE) for staging liver fibrosis and inflammation in patients with hepatocellular carcinoma (HCC) who then undergo surgery and to determine the optimal locations for measurement. In total, 106 patients were enrolled in this prospective study from March 2017 to May 2018. Two-dimensional SWE was used to measure liver stiffness (LS) in each patient 0-1, 1-2 and 2-5 cm from the tumor border (groups 1, 2 and 3, respectively). Spearman's correlation was used to evaluate the relationships between LS and hepatic fibrosis and between LS and inflammation. Receiver operating characteristic curve (ROC) analysis was used to evaluate the diagnostic accuracy of 2D-SWE. The technical success rate of SWE in tissue distant from the tumor (group 3) was significantly higher than that in peri-tumoral tissue (groups 1 and 2) (p < 0.001). Moreover, the area under the ROC for diagnosing cirrhosis (F4) and severe inflammation (A3) was higher for group 3 than for groups 1 and 2. Our results suggest that 2D-SWE is a helpful approach to assessment of hepatic fibrosis in HCC patients before hepatic resection. We found that to achieve a superior success rate and preferable diagnosis accuracy for patients with HCC, LS measurement should be performed 2-5 cm from the tumor margin.

Background and aims Cohort studies found blood lipid traits were associated with the risk of chronic kidney disease (CKD). We aimed to investigate whether blood lipid traits were causally associated with the risk of CKD in the Chinese. Methods 15,244 participants without kidney disease and cancer from the Dongfeng-Tongji cohort were recruited in 2008–2010 in Shiyan City, China. Blood total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), and triglyceride (TG) levels were measured. 5251 participants had genotype data and were included in the Mendelian randomization analysis. Incident CKD was defined as estimated glomerular filtration rate Results Various blood lipid traits were associated with CKD risk, and the odds ratios (95% confidence intervals) for incident CKD comparing the extreme quartiles were 1.45 (1.24–1.70) for TG, 1.26 (1.08–1.46) for nonHDL-c, 2.21 (1.91–2.57) for TC:HDL-c ratio, 2.14 (1.83–2.51) for TG:HDL-c ratio, and 0.47 (0.40–0.55) for HDL-c. The Mendelian randomization analysis indicated that 1 mmol/l increase in the genetic predicted blood TG level was associated with a 5% (95% confidence interval, 0–10%) higher risk of CKD. Conclusions Although blood levels of HDL-c, TG, nonHDL-c, TC:HDL-c ratio, and TG:HDL-c ratio were observed to be associated with incident CKD, the Mendelian randomization analysis provided genetic evidence to support causal relation for blood TG level only.

This study examined the association between digoxin use and subsequent psoriasis risk using a population-based database in Taiwan. This cohort study enrolled 15 545 digoxin users and 15 545 propensity score-matched non-users from the Taiwan National Health Insurance Research Database. Each patient was independently followed up for 5 years to confirm whether they had been diagnosed with psoriasis. Cox proportional hazard regression was used to estimate psoriasis risk among digoxin users. Subgroup and sensitivity analyses were also performed. The psoriasis incidence rates were 3.02 and 2.27 per 1000 person-years among digoxin users and non-users, respectively. After adjustment for confounders, psoriasis risk was significantly higher among digoxin users than among non-users. Notably, in most subgroup analyses, digoxin use tended to increase psoriasis risk, particularly among patients with heart failure, diabetes, hypertension and hyperlipidaemia. Moreover, significantly increased psoriasis risk was noted over 2, 3, 4 and 5 years of digoxin use. In conclusion, our findings confirm that digoxin use increases subsequent psoriasis risk. Thus, physicians should be aware of this association and accordingly estimate the risks and benefits of digoxin use. Nevertheless, some patient variables, such as body mass index and obesity, were unavailable in this study. The findings in this study should be elucidated carefully because the potential effects of these factors could not be considered.

Derived from our original nomogram study by using the risk variables from multivariable analyses in the derivation cohort of 1383 patients with extranodal NK/T-cell lymphoma, nasal-type (ENKTCL) who were mostly treated with anthracycline-based chemotherapy, we propose an easily used nomogram-revised risk index (NRI), validated it and compared with Ann Arbor staging, the International Prognostic Index (IPI), Korean Prognostic Index (KPI), and prognostic index of natural killer lymphoma (PINK) for overall survival (OS) prediction by examining calibration, discrimination, and decision curve analysis in a validation cohort of 1582 patients primarily treated with non-anthracycline-based chemotherapy. The calibration of the NRI showed satisfactory for predicting 3- and 5-year OS in the validation cohort. The Harrell’s C-index and integrated Brier score (IBS) of the NRI for OS prediction demonstrated a better performance than that of the Ann Arbor staging system, IPI, KPI, and PINK. Decision curve analysis of the NRI also showed a superior outcome. The NRI is a promising tool for stratifying patients with ENKTCL into risk groups for designing clinical trials and for selecting appropriate individualized treatment.

The aim of this study was to describe ultrasound (US) and contrast-enhanced ultrasound (CEUS) findings immediately and 1 d after percutaneous irreversible electroporation (IRE) of hepatic malignant tumors. Immediately after IRE, the ablation zone was shown to be a gradually expanding hypo-echoic area around the electrodes. The microcirculation of the ablation zone was markedly reduced on CEUS (before vs. immediately after, p0.001), and the macrocirculation within the ablation zone was preserved. At 1 d after IRE, the ablation zones lost their hypo-echogenicity to become iso-echoic or hyper-echoic (before vs. 1 d after, p = 0.004; immediately after vs. 1 d after, p = 0.002). At this time, further elimination of microcirculation was confirmed on CEUS (before vs. 1 d after, p0.001; immediately after vs. 1 d after, p = 0.003). The size of the ablation zone, which measured by US, was strongly correlated with that measured by CEUS (length: r: = 0.929, width: r = 0.940, p0.001), was significantly enlarged immediately after IRE and shrunk 1 d after IRE.

Background We compared the efficacy and toxicity of three IC regimens (TPF: taxanes, cisplatin, and 5-fluorouracil; TP: taxanes and cisplatin; and PF: cisplatin and 5-fluorouracil) followed by CCRT in locoregionally advanced NPC. Methods The retrospective study involved 1354 patients with newly diagnosed stage III-IVA NPC treated with IC and CCRT. The median follow-up time in our cohort was 50 months. Based on EBV DNA level, all the patients with stage IV were divided into low- (pre-EBV DNA Results A multivariate analysis revealed TPF to be more effective than TP. Among stage III patients, no significant difference in clinical outcome between the different IC regimens was showed, while TPF was associated with significantly better survival conditions in the stage IV patients. A further subgroup analysis revealed that only patients with pre-EBV DNA ≥ 1500 copies could benefit from the application of TPF among stage IV NPC. In terms of acute toxicities, PF was associated with fewer grade 3/4 acute toxicities. Conclusions In low-risk NPC patients, PF-based IC showed similar efficacy as TPF and TP but was associated with fewer grade 3/4 acute toxicities. In high-risk patients, however, the TPF regimen was superior to PF and TP, although grade 3/4 toxicities were more common with the TPF regimen.

Objective: The main aim of this study was to establish a scoring model to predict risk of progression and survival in patients with regionally recurrent nasopharyngeal carcinoma (NPC). Methods: Three hundred and forty-eight patients subjected to neck dissection from 2003 to 2017 were included for study. Clinicopathologic information for each patient was analyzed. Independent prognostic factors were selected using the Cox proportional hazards model and incorporated into the scoring model. Concordance index (C-index) and calibration curves were used to verify discrimination and calibration, respectively and the results validated using bootstrap resampling. Results: Microscopic positive lymph node > 2 [hazard ratio (HR), 2.19; 95% confidence interval (CI), 1.30-3.68; P = 0.003], extranodal extension (HR, 2.75; 95% CI, 1.69-4.47; P < 0.001), and lower neck involvement (HR, 1.78; 95% CI, 1.04-3.04; P = 0.034) were identified from multivariate analysis as independent factors for overall survival (OS). A qualitative 4-point scale was generated to stratify patients into 4 risk groups for predicting OS and progression-free survival (PFS). The novel scoring model demonstrated enhanced discrimination (C-index = 0.69; 95% CI, 0.62-0.76) relative to the original recurrent tumor-node-metastasis (rTNM) staging system (C-index = 0.56; 95% CI, 0.50-0.62), and was internally validated with a bootstrap-adjusted C-index of 0.70. The calibration curve showed good agreement between predicted probabilities and actual observations. Conclusions: The scoring system established in this study based on a large regionally recurrent NPC cohort fills a gap regarding assessment of risk and prediction of survival outcomes after neck dissection in this population and could be further applied to identify high-risk patients who may benefit from more aggressive intervention.

Patients with recurrent nasopharyngeal carcinoma (NPC) have more co-existing distant metastasis than those of no-recurrence and are more likely to suffer distant metastasis after re-irradiation than patients with newly diagnosed NPC. However, the relationship between radioresistance and distant metastasis and the mechanisms involved in radioresistance-associated metastasis are still unclear. In this study, we proved that C-C motif chemokine ligand 2 (CCL2) expression was significantly elevated in HONE1-IR cells and recurrent NPC tumour. Inhibition of CCL2 enhanced sensitivity to radiotherapy in NPC cells. Moreover, autocrine CCL2 promoted NPC cell adaptive radioresistance, metastasis and epithelial-mesenchymal transition. Additionally, p53 activated CCL2 transcription. High CCL2 expression was highly associated with poorer locoregional recurrence free survival, progression free survival and overall survival in patients with newly diagnosed NPC. Notably, high CCL2 expression was an independent prognostic factor for distant metastasis free survival in recurrent NPC patients. Our results provide insights into the autocrine signalling mechanisms of CCL2 and suggest that inhibition of autocrine CCL2 may be a candidate treatment strategy for management of radioresistant NPC.

The present study explored the protective effect of exogenous hydrogen sulfide (H2S) on lipopolysaccharide (LPS)-induced acute kidney injury (AKI) and the underlying mechanisms. To establish an AKI injury mouse model, LPS (10 mg/kg) was intraperitoneally injected into mice pretreated with 0.8 mg/kg sodium hydrosulfide hydrate (NaHS), an H2S donor. The mouse survival rate and the degree of kidney injury were examined. To construct a cell damage model, HK-2 cells were pretreated with different concentrations (0.1, 0.3 and 0.5 mM) of NaHS, and then the cells were stimulated with LPS (1 µg/ml). The cell viability, autophagy, apoptosis levels and the release of inflammatory factors were examined in mouse kidney tissue and HK-2 renal tubular epithelial cells. It was found that pretreatment with NaHS significantly improved the survival rate of septic AKI mice, and reduced the renal damage, release of inflammatory factors and apoptosis. In HK-2 cells, NaHS protected cells from LPS caused damage via promoting autophagy and inhibiting apoptosis and the release of inflammatory factors. In order to clarify the relationship between autophagy and apoptosis and inflammatory factors, this study used 3-methyladenine (3-MA) to inhibit autophagy. The results revealed that 3-MA eliminated the protective effect of NaHS in HK-2 cells and AKI mice. Overall, NaHS can protect from LPS-induced AKI by promoting autophagy and inhibiting apoptosis and the release of inflammatory factors.

NADPH oxidase (NOX) enzymes are involved in a various physiological and pathological processes such as platelet activation and inflammation. Interestingly, we found that the pan-NOX inhibitors VAS compounds (VAS2870 and its analog VAS3947) exerted a highly potent antiplatelet effect. Unlike VAS compounds, concurrent inhibition of NOX1, 2, and 4 by treatment with ML171, GSK2795039, and GKT136901/GKT137831 did not affect thrombin and U46619-induced platelet aggregation. These findings suggest that VAS compounds may inhibit platelet aggregation via a NOX-independent manner. Thus, we aimed to investigate the detailed antiplatelet mechanisms of VAS compounds. The data revealed that VAS compounds blocked various agonist-induced platelet aggregation, possibly via blocking PKC downstream signaling, including IKKβ and p38 MAPK, eventually reducing platelet granule release, calcium mobilization, and GPIIbIIIa activation. In addition, VAS compounds inhibited mouse platelet aggregation-induced by collagen and thrombin. The in vivo study also showed that VAS compounds delayed thrombus formation without affecting normal hemostasis. This study is the first to demonstrate that, in addition to inhibiting NOX activity, VAS compounds reduced platelet activation and thrombus formation through a NOX-independent pathway downstream of PKC. These findings also indicate that VAS compounds may be safe and potentially therapeutic agents for treating patients with cardiovascular diseases.

Key Points Question Does nedaplatin-based concurrent chemoradiotherapy (CCRT) have comparable efficacy to cisplatin-based CCRT in stage II to IVB nasopharyngeal carcinoma? Findings In this 5-year follow-up secondary analysis of a randomized clinical trial of 402 eligible patients, nedaplatin-based CCRT achieved 5-year progression-free survival rates comparable to those in the cisplatin-based CCRT group. Patients in the nedaplatin group also experienced fewer late toxic effects. Meaning These results confirm that nedaplatin-based CCRT can be regarded as an alternative to cisplatin-based CCRT in stage II to IVB nasopharyngeal carcinoma., Importance Nedaplatin-based concurrent chemoradiotherapy (CCRT) regimen at 2 years was noninferior to cisplatin-based regimen in patients with locoregional, stage II to IVB nasopharyngeal carcinoma (NPC) and was associated with fewer late adverse events, but longer-term outcomes and toxicity are unclear. Objective To evaluate the 5-year outcomes and late toxicity profile of nedaplatin-based CCRT in patients with locoregional, stage II to IVB NPC. Design, Settings, and Participants This 5-year follow-up secondary analysis of an open-label, noninferiority, multicenter randomized clinical trial enrolled patients with nonkeratinizing stage II to IVB NPC between January 16, 2012, and July 16, 2014, with a median follow-up duration of 78 months (IQR, 3-99 months). Data analysis was conducted from November 10, 2020, to July 8, 2021. Interventions Patients were randomly assigned (1:1) to receive nedaplatin (100 mg/m2)– or cisplatin (100 mg/m2)–based chemotherapy every 3 weeks for 3 cycles concurrently with intensity-modulated radiotherapy. Main Outcomes and Measures The primary end point was progression-free survival (PFS). Secondary end points were overall survival, distant metastasis–free survival, and locoregional relapse–free survival. Results A total of 402 eligible participants were enrolled (median [IQR] age, 45 [18-65] years; 302 [75.1%] male). Patients were randomly assigned to receive nedaplatin- or cisplatin-based CCRT (n = 201 for each): 196 patients (97.5%) started nedaplatin-based CCRT and 197 patients (98.0%) started cisplatin-based CCRT. Intention-to-treat analysis demonstrated a 5-year progression-free survival rate of 81.4% (95% CI, 75.9%-86.9%) for the cisplatin group and 79.8% (95% CI, 74.1%-85.5%) for nedaplatin group, with a difference of 1.6% (95% CI, −6.3% to 9.5%; P = .002 for noninferiority). No significant survival differences were observed between the cisplatin and nedaplatin groups for 5-year overall survival (89.4% vs 88.8%, P = .63), distant metastasis–free survival (85.9% vs 90.4%, P = .17), and locoregional relapse–free survival (92.6% vs 89.6%, P = .17) rates. The cisplatin group had a higher incidence of grade 3 and 4 auditory toxic effects than the nedaplatin group (35 [17.7%] vs 21 [10.5%], P = .04). Conclusions and Relevance In this secondary analysis of a randomized clinical trial, long-term analysis confirmed that nedaplatin-based CCRT could be regarded as an alternative doublet treatment strategy to cisplatin-based CCRT in stage II to IVB NPC. Trial Registration ClinicalTrials.gov Identifier: NCT01540136, This 5-year follow-up secondary analysis of a randomized clinical trial analyzed survival outcomes and late toxic effects to assess the efficacy of nedaplatin-based concurrent chemoradiotherapy in the treatment of stage II to IVB nasopharyngeal carcinoma.

Background Bone metastasis of colorectal cancer (CRC) often indicates a poor prognosis. Osteolysis can be observed in metastatic sites, implying an aberrant activation of osteoclasts. However, how osteoclastogenesis is regulated in metastatic microenvironment caused by colorectal cancer is still unclear. Methods In this study, mice bone metastatic model of CRC was established through injection of MC-38 or CT-26 cells. BrdU assays showed primary CD115 ( +) osteoclast precursors (OCPs) proliferated at the first 2 weeks. Transcriptomic profiling was performed to identify differentially expressing genes and pathways in OCPs indirectly co-cultured with CRC cells Results The expression of IL4Rα was found to be significantly upregulated in OCPs stimulated by tumor conditioned medium (CM). Further investigation indicated that IL-4 signaling regulated proliferation of OPCs through interacting with type I IL4 receptor, and neutrophils were the main source of IL-4 in bone marrow. The proliferation of OCPs can be inhibited in IL4 deficiency mice. In addition, ERK pathway was activated by IL4/IL4R signaling. Ravoxertinib, an ERK antagonists, could significantly prevent bone destruction through inhibiting the proliferation of OCPs. Conclusion Our study indicates the essential role of IL4/IL4R signaling for the proliferation of OCPs in early metastasis of CRC predominantly through activating ERK pathway, which remarkedly impacts the number of osteoclasts in later stage and leads to osteolytic lesions. Moreover, Ravoxertinib could be a new therapeutical target for bone metastasis of CRC.

Background To evaluate the prognostic value of the apparent diffusion coefficient (ADC) derived from diffusion-weighted magnetic resonance imaging (MRI) and monitor the early treatment response to induction chemotherapy (IC) with plasma EBV DNA in locoregionally advanced nasopharyngeal carcinoma (LA-NPC). Results A total of 307 stage III-IVb NPC patients were prospectively enrolled. All patients underwent MRI examinations to calculate ADC and plasma EBV DNA measurements pretreatment and post-IC. The participants’ ADC value of 92.5% (284/307) increased post-IC. A higher percent change in ADC value (ΔADC%high group) post-IC was associated with a higher 5-year OS rate (90.7% vs 74.9%, p low group. Interestingly, ΔADC% was closely related to the response measured by RECIST 1.1 (p p = 0.037). The AUC significantly increased when post-IC plasma EBV DNA was added to ΔADC% to predict treatment failure. Thus, based on ΔADC% and plasma EBV DNA, we further divided the participants into three new prognostic response phenotypes (early response, intermediate response, and no response) that correlated with disparate risks of death (p = 0.001), disease progression (p p p Conclusion The percentage change in ADC post-IC is indicative of treatment response and clinical outcome. ΔADC% and plasma EBV DNA-based response phenotypes may provide potential utility for early termination of treatment and allow guiding risk-adapted therapeutic strategies for LA-NPC.

Objective Survival from out-of-hospital cardiac arrest (OHCA) often depends on the effective and immediate use of automated external defibrillators (AEDs). Given that there have been few studies about AED use in China, the purpose of this study is to investigate the knowledge and attitudes regarding AED use among the Chinese public, then provide an effective suggestion for AED education strategies and legislation. Method The online survey was conducted among Chinese participants of the First Aid eLearning courses in June 2020. Result A total of 2565 (95.00%) surveys were completed, only 23.46% of respondents with non-medical related respondents reported having attended previous AED training courses. Regarding the basic knowledge of AEDs, few respondents (12.28%, n = 315) could answer all four questions correctly. 95.67% (n = 2454) were willing to learn AED use. Even if without the precondition of being skilled in AEDs, the female was more likely to rescue OHCA patients than the male (p = 0.003). Almost all respondents (96.65%) showed a strong willingness to rescue OHCA patients with training in using AEDs. The top four barriers to rescuing OHCA patients were lack of practical performing ability (60.47%), fear of hurting patients (59.30%), inadequate knowledge of resuscitation techniques (44.19%), and worry about taking legal responsibility (26.74%). Conclusion Our study reflects a deficiency of AED knowledge among the general public in China. However, positive attitudes towards rescuing OHCA patients and learning AED use were observed, which indicates that measures need to be taken to disseminate knowledge and use of AEDs.

Schisandrin A (Sch A) has a protective effect on cardiomyocytes. Circulating miR-155 levels are related to chronic heart failure (CHF). The present study aimed to clarify the role and the molecular mechanism of Sch A in CHF. C57BL/6JGpt mice were used for an isoproterenol (ISO)-induced CHF model to collect heart samples. Echocardiography was employed to detect heartbeat indicators. The degree of myocardial hypertrophy was evaluated based on the measurement of heart weight (HW), body weight (BW) and tibia length (TL) and the observation using hematoxylin-eosin staining. Sprague-Dawley rats were purchased for the separation of neonatal rat ventricular myocytes (NRVMs), which were treated with ISO for 24 h. Transfection regulated the level of miR-155. The viability of NRVMs was detected via MTT assay. The mRNA and protein levels were measured via reverse transcription-quantitative PCR and western blotting and immunofluorescence was used to detect the content of α-smooth muscle actin (α-SMA). Treatment with ISO resulted in rising left ventricular posterior wall thickness, intra-ventricular septum diastole, left ventricular end diastolic diameter, left ventricular end systolic diameter, HW/BW, HW/TL and falling ejection fraction and fractional shortening, the trend of which could be reversed by Sch A. Sch A ameliorated myocardial hypertrophy in CHF mice. In addition, Sch A inhibited ISO-induced upregulated expressions of atrial natriuretic peptide, B-type natriuretic peptide, B-myosin heavy chain and miR-155 in myocardial tissue. Based on the results in vitro, Sch A had no significant effect on the viability of NRVMs when its concentration was

Singapore, a highly urbanized Asian tropical country that experiences periodic dengue outbreaks, is piloting field releases of male Wolbachia-carrying Aedes aegypti mosquitoes with the aim of suppressing urban populations of the primary dengue vector Aedes aegypti. This study proposes and assesses a model to explain the roles of hesitancy and receptivity towards Project Wolbachia–Singapore in influencing reactive mosquito prevention behaviors (reactive behaviors) towards the release of Wolbachia-Aedes mosquitoes for residents living in the release sites. Interestingly, both hesitancy and receptivity predicted greater instances of reactive behaviors. The model also examines the roles of general knowledge about Wolbachia technology, perceived severity of mosquito bites, perceived density of mosquitoes, and social responsibility as predictors of hesitancy, receptivity, and reactive behaviors towards the release of Wolbachia-Aedes mosquitoes. Hesitancy towards the project mediated the effects of general knowledge, perceived severity of mosquito bites, and perceived density of mosquitoes on reactive behaviors towards the releases, although receptivity towards the project did not. Having less knowledge about Project Wolbachia–Singapore was associated with higher hesitancy towards the project and higher likelihood of performing reactive behaviors towards the releases. Individuals who perceive mosquito bites to be more severe and think that there are more mosquitoes in their living environments were also more likely to be hesitant about the project and practice reactive behaviors. However, both hesitancy and receptivity towards the project mediated the effect of social responsibility on reactive behaviors. Receptivity towards the project was driven by social responsibility, which was also associated with reduced hesitancy towards the project. Our findings suggest that, to address the hesitancy reported by a minority of participants, future outreach efforts should focus on strengthening the public’s sense of social responsibility and on tailored education campaigns targeting groups with low levels of knowledge of the project.

To compare the prognosis and adverse effects of induction or adjuvant chemotherapy (IC or AC) plus concurrent chemoradiotherapy (CCRT) versus CCRT alone in paediatric nasopharyngeal carcinoma (NPC) patients in the intensity-modulated radiotherapy (IMRT) era.549 patients diagnosed from 2005 to 2021 were enrolled. Our primary endpoint was progression-free survival (PFS). The recursive partitioning analysis (RPA) was applied to derive a risk stratification system. Kaplan-Meier survival curves were used to assess the cumulative survival rates, and cox analysis was applied to evaluate the relationship between variables and endpoints.The RPA-based risk stratification identified three different risk groups. In the intermediate-risk (stage IVa and EBV4000 copies/ml) group, patients who received IC followed by CCRT achieved a significantly better 3-year PFS rate than those treated with CCRT alone (87.35% versus 75.89%; P = 0.04). But survival benefit was not obtained from the additional IC or AC in the low-risk (stage II-III and EBV4000 copies/ml) or high-risk (stage II-IVa and EBV≥4000 copies/ml) group. The most common grade 3 or 4 adverse events in patients treated with CCRT, IC + CCRT, and CCRT + AC were neutropenia (8.1%, 33.0% versus 36.9%, respectively) and leukopenia (14.1%, 26.8% versus 32.3%, respectively) with statistically significant difference.Paediatric NPC patients in the intermediate-risk group treated with IC followed by CCRT had significantly better PFS compared with patients treated with CCRT alone. And the overall incidence of acute adverse events in patients treated with IC or AC plus CCRT was higher than in patients treated with CCRT alone.

Background: Our previous study indicates that Brucea javanica oil (BJO) is beneficial for treatment of ulcerative colitis (UC), and that quassinoids in particular brusatol are bioactive components. However, it is still uncertain whether or not other components in BJO, such as oleic acid and fatty acids, have anti-UC effect.Purpose: The present study aimed to compare the anti-UC effects between brusatol-enriched BJO (BE-BJO) and brusatol-free BJO (BF-BJO), and to explore the effects and mechanisms of BE-BJO on colon inflammation and intestinal epithelial barrier function.Methods: Balb/C mice received 3% (wt/vol) DSS for one weeks to establish the UC model. Different doses of BE-BJO, BF-BJO or BJO were treated. Body weight and colon length were measured. Disease activity index (DAI) and histological analysis were evaluated. The levels of pro-inflammatory cytokines in the colon tissues were measured by enzyme linked immunosorbent assay (ELISA). The expressions of tight junction proteins were tested to investigate the intestinal epithelial barrier function. The effects of BE-BJO on NF-κB and RhoA/ROCK pathways were studied.Results: BE-BJO alleviated DSS-induced loss of body weight, increase of DAI and shortening of colon, whereas BF-BJO did not have these protective effects. BE-BJO treatment improved the morphology of colon tissue, inhibited the production and release of pro-inflammatory cytokines including TNF-α、 IFN-γ、 IL-6 and IL-1β in the colon tissue, as well as reversed the decreased expressions of ZO-1, Occludin, Claudin-1and E-cadherin induced by DSS, but augmented Claudin-2 expression. Mechanistically, BE-BJO repressed phosphorylation of NF-κB subunit p65, suppressed RhoA activation, downregulated ROCK, and prevented phosphorylation of myosin light chain (MLC) in DSS-treated mice.Conclusions: This work demonstrated that BE-BJO could ameliorate DSS-induced UC by preventing colon inflammation and enhancing intestinal epithelial barrier function, probably via suppression of NF-κB and RhoA/ROCK signaling pathways. These findings confirm that quassinoids are active compounds from BJO and suggest the therapeutic potential of quassinoids and BE-BJO in the treatment of UC.

Oesophageal cancer is the sixth leading cause of cancer death worldwide. This nationwide study analyses the survival results of oesophageal cancer under multidisciplinary team (MDT) care. We enrolled oesophageal cancer patients diagnosed between 2010 and 2015 with follow-up for at least 1 year. This study performed propensity score matching with a ratio of 1:1 between MDT participants and non-MDT participants. We performed conditional Cox proportional hazards model to research relative risk of survival and associated factors of survival. The adjusted survival curves were plotted. 8184 newly diagnosed oesophageal cancer patients were included. The favourable survival factors include participant status of MDT, gender, monthly salary, urbanization level, other catastrophic illness, stage of cancer, treatment methods, and service volume of physicians (P

Although disease susceptibility is known to differ between men and women, it is controversial whether the efficacy of immune checkpoint inhibitors for malignancies also differs between the sexes. We conducted a meta-analysis to explore the impact of sex on immune checkpoint inhibitor treatment outcomes. We searched PubMed, Embase and the Cochrane Library databases from inception to October 1, 2020 for randomized controlled trials of immune checkpoint inhibitors with hazard ratios (HRs) stratified by sex. We calculated the pooled HRs for men and women using the ln(HR), and assessed the heterogeneity between the two estimates through an interaction test. In total, 22,268 patients from 39 randomized controlled trials were included. Immune checkpoint inhibitors yielded better overall survival than conventional agents in both men (HR: 0.75, 95% confidence interval [CI]: 0.71-0.80) and women (HR: 0.77, 95% CI: 0.70-0.85). Progression-free survival benefits were also observed in both men (HR: 0.64, 95% CI: 0.58-0.70) and women (HR: 0.67, 95% CI: 0.58-0.77) treated with immune checkpoint inhibitors. No sex differences in the response to immune checkpoint inhibitors were found when overall survival and progression-free survival were used as the endpoints.

Some previous literature indicated an association between cardiovascular diseases and erectile dysfunction (ED). This case-control study purposed to evaluate the association between prior mitral valve prolapse (MVP) and ED using data from the Taiwan National Health Insurance Research Dataset. In this study, 48,755 patients with ED were identified as cases, and 195,020 propensity score-matched patients without ED were selected as controls. Conditional logistic regressions were conducted to evaluate the odds ratios (ORs) for previous MVP between cases and the matched controls. In all sampled patients, 4,565 (1.87%) patients had MVP before the index date. MVP was found in 1,304 (2.67%) cases and in 3,261 (1.67%) matched controls. Patients with ED had a significantly higher occurrence of MVP than the controls. In addition, after propensity score matching, a conditional logistic regression analysis showed that the OR of previous MVP for patients with ED was 1.63 (95% confidence interval [CI] 1.52 to 1.74) compared to the matched controls. The ORs of previous MVP for patients with ED aged ≤65 years and those >65 years were 1.68 (95% CI 1.56 to 1.81) and 1.49 (95% CI 1.30 to 1.70), respectively, compared with the matched controls. We found that patients with erectile dysfunction had significantly higher odds of previous MVP compared with matched control subjects without ED regardless of the age group.

The typical phenotype of arthrogryposis, renal dysfunction, and cholestasis (ARC) syndrome involves three cardinal symptoms as the name describes, harboring biallelic mutations on VPS33B or VIPAS39. Except for ARC syndrome, low gamma-glutamyltransferase (GGT) cholestasis often implies hereditary hepatopathy of different severity; however, some remain undiagnosed. Several monogenic defects typically with multiorgan manifestations may only present liver dysfunction at times, such as DGUOK defect and AGL defect. Previously, four VPS33B mutated cases were reported without arthrogryposis, or with less severe symptoms and longer lifespan, indicating the possibility of incomplete ARC phenotype of isolated hepatopathy. So we retrospectively reviewed all patients with confirmed VPS33B/VIPARS39 defect in our center and identified three presenting isolated low-GGT cholestasis with intractable pruritus. Distinguished from others with typical ARC phenotype, these patients did not suffer the other two typical characteristics, survived much longer, and shared a novel missense VPS33B variation c.1726T>C, p.Cys576Arg, causing declined protein expression and abolished interaction with VIPAS39 in-vitro. Serum bile acid profiles of our VPS33B/VIPAS39 mutated patients revealed similar changes to primary defect of bile salt export pump, among which those with isolated cholestasis phenotype had a higher level of total secondary bile acids than that with typical ARC phenotype, indicating the partial residual function of VPS33B.

BACKGROUND Ultrasonography-guided percutaneous drainage for pancreatic fluid collections is associated with a high recurrence rate and endoscopic ultrasonography (EUS)-guided drainage is a valuable approach. Our aim was to compare the efficacy and safety of percutaneous and EUS-guided drainage for the recurrent pancreatic fluid collections. MATERIAL AND METHODS A retrospective analysis of percutaneous-guided and EUS-guided procedures for pancreatic fluid collections drainages at a single tertiary care center between February 2017 and May 2018 was performed. Treatment success, adverse events, recurrence, need for surgery, length of hospital stays, and number of follow-up computed tomography (CT) scan were assessed. RESULTS A total of 119 pancreatic fluid collections treated with initial percutaneous drainage were included in this study and 35 patients had recurrent pancreatic fluid collections. Recurrent patients were classified based on drainage method: EUS-guided drainage (18 patients) and the second percutaneous drainage (17 patients). EUS-guided drainage revealed a shorter length of hospital stays (P

Object To ascertain the treatment effect of concurrent chemotherapy (CCT) in stage II‐III nasopharyngeal carcinoma (NPC) patients with different Epstein‐Barr virus (EBV) DNA level in intensity‐modulated radiotherapy (IMRT) era. Methods A total of 2742 patients diagnosed with stage II‐III NPC were involved in this study. Patients received IMRT with/without CCT. Overall survival (OS) was the primary endpoint. Receiver operating characteristics curve was used to determine the cut‐off value of pre‐DNA based on OS. After propensity score matching, the role of CCT was explored in patients with different EBV DNA level. Results In our cohort, the cut‐off value of pre EBV DNA was 1460 copies/mL (area under curve [AUC], 0.695‐0.769; sensitivity, 0.766; specificity, 0.599). Patients with high EBV DNA level showed poor survival in OS, progression free survival (PFS), locoregional relapse‐free survival (LRFS) and distant metastasis‐free survival (DMFS). In patients with EBV DNA level >1460 copies/mL, the concurrent chemoradiotherapy (CCRT) group achieved higher 3‐year OS compared with IMRT groups. However, the CCRT and IMRT groups showed comparable OS in patients with EBV DNA ≤1460 copies/mL. In multivariate analyses, CCT was a protective factor for OS, PFS, and LRFS in high‐risk patients (EBV DNA level >1460 copies/mL), while not an independent prognostic factor among the low‐risk patients (EBV DNA level ≤1460 copies/mL). Conclusion Pre‐EBV DNA could be a useful tool to guide individualized treatment for stage II‐III NPC patients. Additional CCT to IMRT improved the survival for patients with high pre‐EBV DNA, while those with low pre‐EBV DNA could not.

Background The morbidity of knee arthritis is increasing among aged people and total knee arthroplasty has been its mainstream treatment to date. Postoperative rehabilitation is an important part of the procedure. However, the intense pain during the functional exercise involved has always been a challenge for both patients and health care professionals. The aim of this study is to test the analgesic effect of a mixture of nitrous oxide/oxygeb (1:1) inhalation for patients who are doing functional exercise 1 month after total knee arthroplasty. Methods/design This double-blind, randomized, placebo-controlled study will be implemented in the Rehabilitation Department in the General Hospital of Ningxia Medical University. Patients aged between 50 and 75 years who underwent a primary unilateral total knee arthroplasty are eligible for inclusion. The key exclusion criteria include: epilepsy, pulmonary embolism, intestinal obstruction, aerothorax. The treatment group (A) will receive a pre-prepared nitrous oxide/oxygen mixture plus conventional treatment (no analgesics), and the control group (B) will receive oxygen plus conventional treatment (no analgesics). Patients, physicians, therapists, and data collectors are all blind to the experiment. Assessments will be taken immediately after functional exercise begins (T0), 5 min (T1) after functional exercise begins, and 5 min after functional exercise has finished (T2). Patients will be randomly allocated between a treatment group (A) and a control group (B) in a ratio of 1:1. Primary outcome, including pain severity in the procedure, will be taken for each group. Secondary outcomes include blood pressure, heart rate, oxygen saturation, side effects, knee joint range of motion, Knee Society Score (KSS), rescue analgesia need, and satisfaction from both therapists and patients. Discussion This study will focus on exploring a fast and efficient analgesic for patients who are doing functional exercise after total knee arthroplasty. Our previous studies suggested that the prefixed nitrous oxide/oxygen mixture was an efficacious analgesic for the management of burn-dressing pain and breakthrough cancer pain. The results of this study should provide a more in-depth insight into the effects of this analgesic method. If this treatment proves successful, it could be implemented widely for patients doing functional exercise in the rehabilitation department. Trial registration ChiCTR-INR-17012891. Registered on 6 October 2017. Electronic supplementary material The online version of this article (10.1186/s13063-019-3472-7) contains supplementary material, which is available to authorized users.

Background Dietary intakes of B vitamins (eg, folate) are related to cognitive function according to epidemiological studies in western countries. But prospective studies in Asian populations are scarce. This study evaluated the relationships of dietary intakes of six B vitamins in midlife with cognitive impairment in old age in a Chinese population living in Singapore. Methods This study included 16,948 participants from the Singapore Chinese Health Study, a population-based prospective cohort. Baseline dietary intakes of B vitamins were assessed using a validated 165-item food frequency questionnaire when the participants were aged 45–74 years (1993–1998). After an average follow-up of 20 years, cognitive function was examined using a Singapore-modified version of Mini-Mental State Examination scale in 2014–2016, and cognitive impairment was defined using education-specific cutoffs. Logistic regression models were applied to estimate the association between B vitamins and cognitive impairment. All the six B vitamins were mutually adjusted in the final model. Results In the 2014–2016 interview, 2,443 participants were defined as cognitive impairment. Riboflavin and folate were significantly and independently associated with cognitive impairment in a dose-dependent manner: the odds ratio (95% confidence interval) comparing the highest with the lowest quartile was 0.82 (0.69, 0.97) for riboflavin and 0.83 (0.70, 0.98) for folate (both p-trend Conclusions Higher dietary intakes of riboflavin and folate in midlife were associated with a lower risk of cognitive impairment in late-life in the Chinese population.

The 3,4-methylenedioxymethamphetamine (MDMA) is a popular recreational drug, which ultimately leads to serotonergic (5-HT) neurotoxicity and psychiatric disorders. Previous in vitro studies have consistently demonstrated that MDMA provokes autophagic activation, as well as damage of 5-HT axons and nerve fibers. So far, whether autophagy, a well-conserved cellular process that is critical for cell fate, also participates in MDMA-induced neurotoxicity in vivo remains elusive. Here, we first examined time-course of autophagy-related changes during repeated administration of MDMA (10 mg/kg s.c. twice daily for 4 consecutive days) using immunofluorescent staining for tryptophan hydroxylase and microtubule-associated protein 1 light chain 3 beta in rats. We also evaluated the protective effects of 3-methyadanine (3-MA, an autophagy inhibitor, 15 mg/kg i.p.) against MDMA-induced acute and long-term reductions in serotonin transporters (SERT) density in various brain regions using immunohistochemical staining and positron emission tomography (PET) imaging respectively. Plasma corticosterone measurements and forced swim tests were performed to evaluate the depressive performance. The staining results showed that repeated administration of MDMA increased expression of autophagosome and caused reduction in SERT densities of striatum and frontal cortex, which was ameliorated in the presence of 3-MA. PET imaging data also revealed that 3-MA could ameliorate MDMA-induced long-term decreased SERT availability in various brain regions of rats. Furthermore, immobility time of forced swim tests and plasma corticosterone levels were less in the group of MDMA co-injected with 3-MA compared with that of MDMA group. Together, these findings suggest that autophagy inhibition may confer protection against neurobiological and behavioral changes induced by MDMA.

Background The social structure is changing with an increase in the ratio of the older population, resulting in a growing number of older people being faced with singlehood. This study identified and described single older adults’ differing perspectives on new relationships. Method We used a Q methodology approach for data collection and analysis, following in-depth interviews with 10 participants. Q statements were developed through content analysis of the interview data, which were then subjected to Q sorts performed by 49 older adults. A factor analysis was then completed on the collected data using PQ Method software. Results Five factors regarding common attitudes toward pursuing a new partner, which accounted for 53% of the total variance, were obtained in the final model: (1) being single, a companion, and already acquainted with the other person/potential partner; (2) high spiritual compatibility and a caring disposition; (3) an emphasis on physical intimacy and companionship; (4) easily influenced by others’ comments and highly concerned about being alone; and (5) physical and financial independence. Conclusions Clustering older adults according to their attitudes can help in acknowledging their expectations about new relationships in later life. Implications Practitioners can engage in successful consultations based on the recognition. Electronic supplementary material The online version of this article (10.1186/s12877-019-1091-5) contains supplementary material, which is available to authorized users.

BACKGROUND This case-control study aimed to find the relationship between prior statin use and head and neck cancer occurrence using a large population-based database. METHODS This study used claims data from the Taiwan Longitudinal Health Insurance Database. We included 5515 patients with head and neck cancer as cases and 5515 propensity score-matched patients without head and neck cancer as controls. Conditional logistic regressions were performed to investigate the relationship between head and neck cancer and prior statin exposure. RESULTS Of the 11 030 total sampled patients, 16.95% had previously received prescriptions for statins. In addition, statin exposure was found in 15.99% of cases and 17.91% of controls. The logistic regression also revealed that the adjusted odds ratio of prior statin exposure for cases was 0.86 (95% confidence interval: 0.77-0.95) compared to propensity score-matched controls. CONCLUSION This study found an inverse association between statin usage and head and neck cancer occurrence.

Objectives: To elucidate the importance of mutual effects within dyads by examining the contribution of depression on quality of life (QOL) in patients with advanced cancer and their family caregivers (FCs). Sample & Setting: 716 patients with advanced cancer paired with their FCs at two large, private not-for-profit hospices. Methods & Variables: A descriptive, cross-sectional design with the baseline data of a randomized hospice clinical trial was used. Structural equation modeling helped examine four hypotheses by integrating the features of the Actor-Partner Interdependence Model. Variables included QOL and depression. Results: Depression in patients with cancer and their FCs exhibited significant actor effects on an individual’s QOL after controlling for the partner effects. Among the spousal pairs, depression in FCs exhibited a positive partner effect on the functional well-being of patients with cancer, indicating that depressive symptoms occurring in FCs may increase patients’ functional well-being. Implications for Nursing: This study suggests the importance of consistent assessment in emotional well-being for dyads with cancer because their concerns may be transmitted to each other.